What is Glycotoxic Alzheimer's Disease?

by Justin Perr, M.S. Candidate, Dietetic InternNews
Honey dripping from a honey dipper

The role of blood sugar and cognitive decline is becoming much better understood. Sometimes people even refer to this phenomenon as type 3 diabetes. However, here at the Amos Institute we call this glycotoxic Alzheimer's.

So, what is glycotoxic Alzheimer's? Glycotoxic Alzheimer's is a combination of type 1 and type 2, referred to as subtype 1.5. This subtype is characterized by blood sugar dysregulation, chronic inflammation, and hormonal imbalances.

This post will cover the signs, symptoms, and treatment of glycotoxic Alzheimer's.

Causes of Glycotoxic Alzheimer’s

As the subtype 1.5 suggests, glycotoxic Alzheimer's is a combination of type 1 and type 2 Alzheimer's, inflammatory and atrophic. This occurs when chronically high blood sugar causes chronic inflammation and eventually insulin resistance. Therein lies the inflammation from inflammatory Alzheimer's and the hormonal dysregulation from atrophic Alzheimer's. The main distinction here is that blood sugar levels are the main issue. 

The Relationship Between Blood Sugar and Insulin

Whenever we eat a meal with carbohydrates, we absorb it into our blood as sugar. The more carbohydrates we eat at once, the more sugar gets into the blood. So, after a big bowl of rice, our blood sugar concentration goes up considerably. Since our body does not want blood sugar to go too high, it uses a hormone called insulin to lower it. When blood sugar levels elevate, our pancreas is alerted and releases insulin into the blood. Insulin acts as a signal for all of the cells in our body to start soaking up the sugar. This lowers the blood sugar concentration and gives the cells a source of energy. When we constantly consume more carbs than our bodies can handle, the cells start to ignore the insulin signal and do not absorb as much sugar out of the blood [1]. This is called insulin resistance. As a result, the blood sugar concentration continues to rise, and the situation gets worse. When blood sugar levels are chronically elevated, the sugars begin to caramelize onto the proteins in our bloodstream. This process is known as glycation. Thus the term glycotoxic Alzheimer's. These glycated proteins cause inflammation to our body and also contribute to the inflammatory aspect of glycotoxic Alzheimer's.

Insulin Resistance and Glycotoxic Alzheimer’s

If insulin is how the cells in our bodies absorb sugar out of our blood, then what happens to the brain when our bodies become insulin-resistant? Simply put, it begins to starve. The brain primarily runs on sugar, and when the body is insulin resistant, it cannot get as much sugar as it needs [2]. Since there is no actual lack of carbohydrates in the body, there are also no ketone bodies to give the brain an alternate fuel source. The brain begins to panic and starts down a pro-inflammatory pathway in an attempt to downsize the brain [3]. 

Signs and Symptoms of Glycotoxic Alzheimer’s

Many of the signs and symptoms of glycotoxic Alzheimer’s overlap with those of inflammatory and atrophic Alzheimer’s. These can be found in their respective blog posts:

Inflammatory Alzheimer’s

Atrophic Alzheimer’s

The specific lab values that indicate glycotoxic Alzheimer’s are elevated fasting blood glucose, hemoglobin A1c, and fasting insulin. The optimal ranges are listed below:

  • Fasting blood glucose (70-90 mg/dL)
  • Hemoglobin A1c (4.0-5.3%)
  • Fasting insulin (4.0-5.0 μIU/mL)

Treatment of Glycotoxic Alzheimer’s

As with all subtypes of Alzheimer’s, there is no single treatment plan that will work for everyone. However, there are three core steps that are generally applicable to the treatment of glycotoxic Alzheimer’s.

  1. Lower Blood Sugar

The first step to treating glycotoxic Alzheimer’s is to lower blood sugar levels. Though there are many ways this can be accomplished, the main two are through diet and exercise. For diet, this typically requires moderating carbohydrate intake in one way or another. This can be as simple as pairing carbohydrates with fats, protein, and fiber to slow absorption into the bloodstream, or as involved as embarking on a ketogenic diet. These dietary strategies are very individualized and should be discussed with a dietitian. For exercise, simply walking for 10 minutes after a meal can be an incredibly effective way to lower blood sugar. Exercise needs and suggestions vary heavily based on age, metabolic health, and medication.

  1. Improve Insulin Sensitivity

The good news is that if you are working to lower your blood sugar, you are also actively improving insulin sensitivity. However, there are also some extra tips and tricks that may speed up the process if you are already eating and exercising properly. Getting high quality sleep is important for maintaining overall health, but data also suggests that getting appropriate sleep can help to reverse insulin resistance [4]. Additionally, it is important to practice stress management. Cortisol, our stress hormone, can cause insulin resistance [5]. This is why cortisol lowering exercises like meditating can be an important component of a glycotoxic Alzheimer’s treatment plan.

  1. Provide an Alternative Fuel Source

In some cases, it is important to give the brain an alternative fuel source. This is particularly important when the brain cannot properly absorb sugar from the blood due to insulin resistance, and symptoms of cognitive impairment are present. In this case, ketone bodies would be the alternative fuel source [6]. Ketone bodies can be made in the body by following a high-fat, low-carb diet, or by supplementing ketones directly. There are pros and cons with each option, so this is a discussion that is important to have with a trained professional. 

Conclusion

While a common issue, it can be incredibly difficult to repair blood sugar metabolism on your own. If high blood sugar is also accompanied with cognitive impairment, as is the case with glycotoxic Alzheimer’s, it is very important to work with a doctor and dietitian who are trained in the Bredesen Protocol. A trained team will be helpful in developing a functional protocol to optimize blood sugar metabolism while addressing any other root causes of dysfunction.  Contact the Amos Institute today to make an appointment with a dietitian trained in the Bredesen Protocol and functional medicine. 


References:

  1. Galicia-Garcia et al., 2020, 10.3390/ijms21176275
  2. Keller & Craft, 2020, https://doi.org/10.1016/S1474-4422(20)30231-3
  3. Bredesen, D. E. (2017). The end of Alzheimer's: The first program to prevent and reverse cognitive decline. Avery, an imprint of Penguin Random House. 
  4. Mesarwi et al., 2014, 10.1016/j.ecl.2013.05.001
  5. Adam et al., 2010, 10.1210/jc.2010-0322
  6. Henderson, 2008, 10.1016/j.nurt.2008.05.004